The present invention relates to a therapy method and apparatus for generating high-intensity ultrasound with control of cavitation effect, and to the use of this method and apparatus for reducing secondary lobes set up by a periodic-type structure.
It is known that ultrasound therapy, using a piezoelectric transducer driven by sinewave-type electronic signals makes it possible to create tissue lesions through tissue heating due to ultrasound absorption. Furthermore, such tissue lesions can be limited to a specific volume by carrying out therapy using focused ultrasound, which is particularly valuable for achieving effective treatment in cancer therapy such as, for example, cancer of the prostate, breast, brain, etc.
Existing hyperthermia apparatus using ultrasound heats tumors to a moderate temperature of the order of 42.5.degree. C. for a time of the order of one hour.
Since hyperthermia treatment may be insufficient, it can be advantageous to attempt to obtain much higher temperatures, for example of around 80.degree. C., with a view to sensitizing cells or completely destroying them. To achieve this, it is necessary to supply acoustic energy to the tissue over a brief period, generally of the order of a few seconds, in order, notably, to avoid heat loss by natural transfer, notably due to blood circulation, throughout the tissue. Sufficient energy needs to be used and this implies using high ultrasound intensity.
This however brings one up against the technical problems resulting from cavitation phenomena which become even more accentuated as acoustic intensity increases, as has been described in detail by K. Hynynen in "The threshold for thermally significant cavitation in dog's thigh muscle in vivo" published in Ultrasound In Medicine and Biology, vol. 17, No. 2, pages 157-171, (1991).
Acoustic cavitation covers any physical phenomena involving the activity of bubbles or micro-bubbles of gas undergoing movement as a result of an acoustic field.
Two types of cavitation can generally be distinguished:
stable cavitation where the walls of the bubbles are oscillating at the frequency of the ultrasound field without too great a consequence for the surrounding cells, but which considerably disturbs ultrasound transmission by reflecting or scattering incident waves. This phenomenon can appear at very low pressure levels as soon as bubbles are present in the medium; PA1 transitory cavitation where bubbles expand up to their resonant size, and than implode violently. In this case, the energy accumulated by the bubbles is simultaneously released in the form of a shock wave, with intense heat (generally from 1,000.degree. to 20,000.degree. K.) and microjets that can reach speeds of 100 m/s. All this leads to the creation of free radicals and mechanical destruction of surrounding tissue. Generally, this phenomenon appears starting from high incident pressures which thus defines the cavitation threshold. PA1 elementary pulse duration ".theta." 0.1 .mu.s&lt;.theta.&lt;100 .mu.s, ideally about 1 .mu.s, PA1 repetition period T: 1 .mu.s&lt;T&lt;10 s, ideally comprised between 0.5 and 5 s.
Every living medium contains a certain amount of dissolved gas present in the form of bubble micronuclei Under the effect of an ultrasound field, the nuclei expand through a physical phenomenon known as rectified diffusion to reach a critical size known as the Blake threshold.
The inventor showed a while ago in an article entitled "Effects of cavitation in high intensity therapeutic ultrasound" published on pages 1357 to 1360 of volume 2 (1991) of "Ultrasonics Symposium Proceedings" (published by B. R. McAvoy) that the use of intensities that were too high, generally above 3,000 W/cm.sup.2 reduced the therapeutic effects of thermal treatment involving tissue destruction. This phenomenon can be explained by supposing that at these intensities, cavitation bubbles which may appear ahead of the focal spot act as a screen for incident ultrasound waves. Moreover, with the specific aim of reducing cavitation effects, F. J. Fry stated in International Patent application WO-A-89/07909 that it is necessary to inhibit production of micro-bubbles in the primary focal site to avoid lesions appearing outside said site (see page 15 of said Patent application). Under these conditions, it is stated that the intensity should not exceed 300 W/cm.sup.2 at a 1 MHz frequency, or 2,100 W/cm.sup.2 at 4 MHz.
K. Hynynen also showed in the above-cited article that an intensity of 700 W/cm.sup.2 /MHz should be considered as a maximum value to be used in hyperthermia treatment as, at higher levels, cavitation leads to unpredictable energy absorption.
To sum up the state of the art, cavitation hinders penetration of acoustic waves into tissue thus preventing treatment from following predictable lines. Moreover, cavitation can lead to uncontrolled tissue destruction, outside the target volume. It is thus appropriate, regardless of the application envisaged (in other words thermal treatment at high temperature for tissue destruction, or at moderate temperature or hyperthermia), to increase cavitation onset thresholds.
To avoid cavitation, the only recommendations that can be found in the prior art consist either in reducing acoustic intensity, or emitting in a discontinuous manner, using wave trains of determined duration, and respecting a waiting time between the trains, or, yet again, increasing emission frequency.
However, reducing acoustic intensity or using discontinuous emission leads to a loss of acoustic energy transmitted to the medium, which limits temperature rise or increases treatment duration. Furthermore, increasing emission frequency limits the depth of treatment, absorption by tissue being directly proportional to frequency, as described by Daniels et al., in the journal "Ultrasound in Medicine and Biology" vol. 13, No. 9, (1987) in the article entitled "Ultrasonically induced gas bubble production in agar based gels". It should also be noted that, in the prior art, continuous sinewaves are employed for tissue heating, and thus emission duration is far higher than signal period. Usually, insonification of tissue for several seconds at a frequency comprised between 1 and 5 MHz is envisaged.
Certain authors have, on the other hand, considered using acoustic waves of a pulsed type, with a duration of the order of several periods, in other words several microseconds, but for a completely different purpose, specifically either the destruction of concretions (lithotritation), or for diagnosis (Doppler ultrasound scanning).
The cavitation phenomena produced by such pulses have been studied. For example, Fowlkes and Crum in an article entitled "Cavitation threshold measurements for microsecond length pulses of ultrasound" published in J. Acoustic Soc. Am. 83 (6), June 1988, investigates the evolution of cavitation threshold as a function of pulse width and pulse frequency. Similarly, Delius, while studying cavitation produced by lithotripters recommended reducing acoustic wave repetition rates (see "Effects of lithotripter shock waves on tissue and materials", Frontiers on non-linear acoustics, edited by M. F. Hamilton and D. T. Blackstock, Elsevier Science Publishers, London 1990).
However, pulse methods do not make it possible to produce a temperature rise in tissue since each pulse only transports small amount of energy, and the pulses need to be spaced. It is thus not possible to assimilate work done with these waves with the work at the basis of this present invention.